Identification of a dihydroartemisinin-related prognostic signature and its contribution to cancer associated fibroblast of the tumor microenvironment of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by high metastatic potential and a stroma-rich tumor microenvironment (TME). Dihydroartemisinin (DHA) has shown antitumor potential in various cancers, but its therapeutic effects on the TME of PDAC are not yet understood. DHA-related differentially expressed genes (DEGs) were identified by high-throughput RNA sequencing in PDAC cells and utilized to explore the biological functions of DHA. The clinical value of DHA was examined by constructing a prognostic risk model using the TCGA dataset. We identified SERPINB5 as a downstream target of DHA involved in TME remodeling through cancer-associated fibroblast (CAF) regulation. The clinical value of SERPINB5 was validated through prognostic risk modeling and immunohistochemistry staining. Our findings indicate that DHA may affect CAF-mediated TME remodeling. Prognostic risk modeling indicates that DHA was associated with PDAC prognosis, implying its clinical potential. DHA may improve the prognosis of PDAC patients by downregulating the expression of SERPINB5, which may participate in regulating CAFs. This study suggests that DHA might improve the prognosis of PDAC patients, and it may influence the PDAC TME by downregulating SERPINB5, offering new insights into DHA’s antitumor mechanisms and its potential clinical applications in PDAC treatment.